The purpose of the proposed studies is to examine the mechanisms that have been postulated in the development of neurogenic pulmonary edema. Studies will be made in sheep in which lung lymph can be collected to assess the alterations in pulmonary fluid and protein exchange and pulmonary vascular permeability and in cats in which hemorrhagic pulmonary edema can be produced by an increase in intracranial pressure. In sheep, it will be determined whether activation of the sympathetic nervous system elicited by either stellate ganglion stimulation or intracranial hypertension or a large and transient increase in pulmonary microvascular pressure produced by mechanical elevation of left atrial pressure increases the pulmonary endothelial permeability to proteins. In addition, the proposed studies will determine whether sympathetic stimulations and a marked increase in pulmonary microvascular pressure act in concert to produce neurogenic pulmonary edema. These studies will also examine independently the effects of Alpha-adrenergic and Beta-adrenergic stimulation on pulmonary fluid and protein exchange and to test the hypothesis that Beta-adrenergic receptors can modulate the transvascular movement of fluid and protein in states of increased vascular permeability. Small increases in pulmonary microvascular pressure produced by mechanical elevation in left atrial pressure and an ultrastructural tracer, catalase, will be used to test for an increase in the permeability of the pulmonary endothelium to proteins, in sheep. Studies will also describe the sites of increased protein permeability in the pulmonary endothelium and epithelium in the cat model of enurogenic pulmonary edema. Whether the increase in pulmonary epithelial permeability is mediated by direct sympathetic stimulation or a large increase in pulmonary microvascular pressure will also be examined in cats. Microperoxidase and horseradish per-oxidase will be used as ultrastructural tracers to demonstrate an increase in pulmonary epithelial permeability. Since the above studies will independently and collectively examine the hemodynamic and non-hemodynamic mechanisms postulated in the development of neurogenic pulmonary edema, the studies will be of value in defining the pathogenesis of neurogenic pulmonary edema.